Current Status of Novel Biomarkers for the Diagnosis of Acute Kidney Injury: A Historical Perspective

Abstract

Acute kidney injury (AKI) is a common and serious medical condition associated with significant increases in morbidity, mortality, and cost of care. Because of the high incidence and poor outcomes associated with AKI, there has been significant interest in the development of new therapies for the prevention and treatment of the disease. A lack of efficacy in drug trials led to the concern that AKI was not being diagnosed early enough for an effective intervention and that a rise in serum creatinine itself is not a sensitive-enough marker. Researchers have been searching for novel biomarkers that can not only assess a decline in kidney function but also demonstrate structural damage to the kidney and at time points earlier than increases in serum creatinine measurements allow. Over the past 10 years, there have been 3300 new publications and hundreds of new biomarkers investigated, yet concern still remains regarding AKI biomarker performance. The AKI biomarkers are yet to be widely utilized in clinical practice, leading some to question whether AKI biomarkers will ever reach their initial promise. However, we believe that biomarkers are an important part of current and future AKI research and clinical management. In this review, we compare the historical contexts of acute myocardial ischemia and AKI biomarker development to illustrate the progress that has been made within AKI biomarker research in a relatively short period of time and also to point out key differences between the disease processes that have been barriers to widespread AKI biomarker adoption. Finally, we discuss potential paths by which biomarkers can lead to appropriate AKI treatment responses that lower morbidity and mortality.

Analysis of Spatiotemporal Urine Protein Dynamics to Identify New Biomarkers for Sepsis-Induced Acute Kidney Injury

“…In addition, several notable drug trial failures raised concerns that AKI was not diagnosed early enough for effective intervention and that a rise in serum creatinine itself is not a sensitive enough marker (Griffin et al, 2018). Biomarkers have been proven to be important tools for current and future AKI research and clinical management (Griffin et al, 2019). Novel biomarkers can not only enable assessment of declines in kidney function but also indicate structural damage in the kidneys at earlier time points than increases in serum creatinine.…”

Investigating subtle kidney injury in primary hyperparathyroidism by means of sensitive and specific biomarkers

“…With the aim of capturing abnormalities preceding the decrease in GFR, novel biomarkers of kidney injury have been developed showing a high sensitivity in detecting the early kidney damage in several conditions . Studies in humans mainly focused on the use of markers of kidney injury in different emergency settings, as critically ill patients, heart failure, after major cardiac surgery, kidney transplantation or cisplatin administration, and in the evaluation of contrast‐induced acute kidney injury . Elevation of many of the novel biomarkers has been described in animal and human studies of drug‐induced kidney toxicity [eg kidney injury molecule‐1 (KIM‐1), β2‐microglobulin (B2M), cystatin C, interleukin‐18 (IL‐18), neutrophil gelatinase‐associated lipocalin, (NGAL)] …”

“…Fewer data are reported in chronic disease . The overall data showed that the assessment of a panel of the novel biomarkers is useful in the early detection of kidney injury, with high prognostic value . As far as endocrine disease, recent works have shown that the assessment of biomarkers of tubular damage could have diagnostic value in screening patients for diabetic kidney disease .…”

“…11,12 Studies in humans mainly focused on the use of markers of kidney injury in different emergency settings, as critically ill patients, heart failure, after major cardiac surgery, kidney transplantation or cisplatin administration, and in the evaluation of contrast-induced acute kidney injury. 11,13 Elevation of many of the novel biomarkers has been described in animal and human studies of drug-induced kidney toxicity [eg kidney injury molecule-1 (KIM-1), β2-microglobulin (B2M), cystatin C, interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin, (NGAL)]. 14 Fewer data are reported in chronic disease.…”

“…15,16 The overall data showed that the assessment of a panel of the novel biomarkers is useful in the early detection of kidney injury, with high prognostic value. 11,13 As far as endocrine disease, recent works have shown that the assessment of biomarkers of tubular damage could have diagnostic value in screening patients for diabetic kidney disease. 16 Additionally, animal data have shown a direct association between specific biomarkers, mechanism of renal damage (ischaemic, toxic, inflammatory, etc) and the level of the nephron interested by injury.…”